The flavonol rutin has been shown to possess antioxidant and iron chelating properties in vitro and in vivo. These dual properties are beneficial as therapeutic options to reduce iron accumulation and the generation of reactive oxygen species resultant from excess free iron. The effect of rutin on iron metabolism has been limited to studies performed in wild type mice either injected or fed high iron diets. The effect of rutin on iron overload caused by genetic dysregulation of iron homeostasis has not yet been investigated. In this study we examined the effect of rutin treatment on tissue iron loading in a genetic mouse model of iron overload, which mirrors the iron loading associated with Type 3 hereditary hemochromatosis patients who have a defect in Transferrin Receptor 2. Male Transferrin Receptor 2 knockout mice were administered rutin via oral gavage for 21 continuous days. Following treatment, iron levels in serum, liver, duodenum, and spleen were assessed. In addition, hepatic ferritin protein levels were determined by western blotting, and expression of iron homeostasis genes by quantitative real-time PCR. Rutin treatment resulted in a significant reduction in hepatic ferritin protein expression and serum transferrin saturation. In addition, trends towards decreased iron levels in the liver and serum, and increased serum unsaturated iron binding capacity were observed. This is the first study to explore the utility of rutin as a potential iron chelator and therapeutic in an animal model of genetic iron overload.
Ablation of Na
+
/H
+
exchanger‐3 prevents iron loading in the Hfe mouse model of hereditary hemochromatosis
